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Abstract Digital pathology and image analysis potentially provide greater accuracy, reproducibility and standardisation of pathology‐based trial entry criteria and endpoints, alongside extracting new insights from both existing and novel features. Image analysis has great potential to identify, extract and quantify features in greater detail in comparison to pathologist assessment, which may produce improved prediction models or perform tasks beyond manual capability. In this article, we provide an overview of the utility of such technologies in clinical trials and provide a discussion of the potential applications, current challenges, limitations and remaining unanswered questions that require addressing prior to routine adoption in such studies. We reiterate the value of central review of pathology in clinical trials, and discuss inherent logistical, cost and performance advantages of using a digital approach. The current and emerging regulatory landscape is outlined. The role of digital platforms and remote learning to improve the training and performance of clinical trial pathologists is discussed. The impact of image analysis on quantitative tissue morphometrics in key areas such as standardisation of immunohistochemical stain interpretation, assessment of tumour cellularity prior to molecular analytical applications and the assessment of novel histological features is described. The standardisation of digital image production, establishment of criteria for digital pathology use in pre‐clinical and clinical studies, establishment of performance criteria for image analysis algorithms and liaison with regulatory bodies to facilitate incorporation of image analysis applications into clinical practice are key issues to be addressed to improve digital pathology incorporation into clinical trials.

Abstract Clinical trials rely on multidisciplinary teams for successful delivery. Pathologists should be involved in clinical trial design from the outset to ensure that protocols are optimised to deliver maximum data collection and translational research opportunities. Clinical trials must be performed according to the principles of Good Clinical Practice (GCP) and the trial sponsor has an obligation to ensure that all of the personnel involved in the trial have undergone training relevant to their role. Pathologists who are involved in the delivery of clinical trials are often required to undergo formal GCP training and may additionally undergo Good Clinical Laboratory Practice training if they are involved in the laboratory analysis of trials samples. Further training can be provided via trial‐specific investigator meetings, which may be either multidisciplinary or discipline‐specific events. Pathologists should also ensure that they undertake External Quality Assurance schemes relevant to the area of diagnostic practice required in the trial. The level of engagement of pathologists in academia and clinical trials research has declined in the United Kingdom over recent years. This paper recommends the optimal training and accreditation for pathologists undertaking clinical trials activities with the aim of facilitating increased engagement. Clinical trials training should ideally be provided to all pathologists through centrally organised educational events, with additional training provided to pathologists in training through local postgraduate teaching. Pathologists in training should also be strongly encouraged to undertake GCP training. It is hoped that these recommendations will increase the number of pathologists who take part in clinical trials research in order to ensure a high level and standard of data collection and to maximise the translational research opportunities.

Abstract While pathologists have always played a pivotal role in clinical trials ensuring accurate diagnosis and staging, pathology data from prognostic and predictive tests are increasingly being used to enrol, stratify and randomise patients to experimental treatments. The use of pathological parameters as primary and secondary outcome measures, either as standalone classifiers or in combination with clinical data, is also becoming more common. Moreover, reporting of estimates of residual disease, termed ‘pathological complete response’, have been incorporated into neoadjuvant clinical trials. Pathologists have the expertise to deliver this essential information and they also understand the requirements and limitations of laboratory testing. Quality assurance of pathology‐derived data builds confidence around trial‐specific findings and is necessarily focused on the reproducibility of pathological data, including ‘estimates of uncertainty of measurement’, emphasising the importance of pathologist education, training, calibration and demonstration of satisfactory inter‐observer agreement. There are also opportunities to validate objective image analysis tools alongside conventional histological assessments. The ever‐expanding portfolio of clinical trials will demand more pathologist engagement to deliver the reliable evidence‐base required for new treatments. We provide guidance for quality assurance of pathology scoring and reporting in clinical trials.

Plain English summary Young people with cancer are often described as ‘hard to reach’, ‘difficult to engage’ and/or ‘vulnerable’. Consequently, they are often over looked for patient and public involvement activities. We set out to involve young people with cancer to work as co-researchers in the design of the largest ever study of young people with cancer, called BRIGHTLIGHT. In the 10 years since the BRIGHTLIGHT feasibility work began we have involved more than 1200 young people as co-researchers, collaborators, consultants and dissemination partners. We chronicle the key points of this 10-year journey, sharing our success, describing our challenges and the solutions we put in place; sharing also what worked and did not work. Here we share some of these experiences of involving young people in this research and offer some practical advice for those looking to do the same. Abstract Background Young people with cancer, broadly those aged 13–24 years at diagnosis, warrant special attention; physiological and psychological growth creates complex psychosocial needs which neither adult nor child systems are suitably designed to deal with. Resulting from these needs, they are often described as ‘vulnerable’, ‘hard to reach’ and ‘difficult to engage’, and consequently are often over looked for patient and public involvement/engagement (PPIE) roles. In our study ‘BRIGHTLIGHT’, we set out to evaluate whether specialist care for young people adds value, ensuring young people were central to our PPIE activities. We believe that BRIGHTLIGHT is unique as a very large study of young people with cancer which has successfully overcome the challenges of including young people in the research process so we are confident that they have influenced every aspect of study design, conduct and dissemination. Methods We chronicle a period of 10 years, over which we describe our approach and our methods to involving young people in PPIE activities in BRIGHTLIGHT. We describe the feasibility work, study set up, conduct and dissemination of our findings, and weave through our story of PPIE to illustrate its benefits. Through the narration of our experience we highlight significant points that both influenced and changed our direction of travel. We reflect on our experiences and offer some practical advice for those looking to do the same. Results In the 10 years since the BRIGHTLIGHT feasibility work began we have involved more than 1200 young people. Their contributions have been isolated and mapped over a 10-year period. We begin at an early step of identifying what research questions to prioritize, we then plot PPIE activities for one of these research priorities, place of care, which evolved into BRIGHTLIGHT. We document steps along the way to evidence the impact of this involvement. Conclusions Young people can make a valuable contribution to healthcare research given adequate support from the research team. Although some challenges exist, we propose that the benefits to young people, researchers and the study considerably outweigh these challenges and PPIE with young people should be integrated in all similar research studies.